Immunotherapy in Combination With Chemoradiotherapy in Unresectable Locally Advanced Esophageal Cancer

Esophageal Squamous Cell Carcinoma Clinical Trial

Official title:

A Phase I/II Multicenter Study Evaluating the Efficacy and Safety of Induction Immunochemotherapy Followed by Concurrent Immuno-Chemoradiotherapy in Unresectable Locally Advanced Esophageal Squamous Cell Cancer(SCR-ESCC-02)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06173986
• Other study ID #: SCR-ESCC-02
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: January 10, 2023
• Est. completion date: December 30, 2027

Study information

• Verified date: December 2023
• Source: Shanghai Chest Hospital
• Contact: Wen Yu, M.D
• Phone: 021-22200000-3203
• Email: yuzhiwen0827[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

SCR-ESCC-02 is a multicenter, phase I/II clinical study to investigate the safety and efficacy of induction immunochemotherapy followed by concurrent chemoradiotherapy with anti-PD-1 therapy in patients diagnosed with locally advanced, unresectable esophageal cancer.

Description:

Immunotherapy has shown promising results in advanced esophageal cancer, but its optimal integration into the management of unresectable locally advanced disease remains uncertain. The significant tumor regression and reduced tumor residual achieved through immunochemotherapy offer an opportunity to enhance the effectiveness of subsequent radiotherapy. This phase I/II clinical study aims to investigate the efficacy and safety of induction immunochemotherapy followed by concurrent chemoradiotherapy with anti-PD-1 for patients with unresectable locally advanced esophageal cancer. The study's co-primary endpoints are progression-free survival (PFS) and treatment completion rate.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: December 30, 2027
• Est. primary completion date: December 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Age between 18 and 75 years.

2. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.

3. Clinical stage meeting the criteria of T1N+M0 or T2-4aN0-3M0 based on the 8th UICC-TNM classification.

4. Ineligibility for surgical resections due to patients' unwillingness for surgery, technically unresectable disease, or being medically unfit for surgery.

5. No prior anti-tumor treatment, including surgery, radiotherapy, chemotherapy, immunotherapy, or targeted therapy.

6. Adequate hematological, pulmonary, cardiac, hepatic, renal, and thyroid function.

7. Willingness to use contraception with an adequate method throughout the study.

8. Documented informed consent.

Exclusion Criteria:

1. History of malignant disease within the 5 years preceding enrollment or presence of other malignant tumors or non-squamous cell carcinoma components.

2. High risk of gastrointestinal bleeding, esophageal fistula, or esophageal perforation as determined by the investigators.

3. Weight loss exceeding 20% within the 90 days prior to the first day of drug administration.

4. Presence of long-standing unhealed wounds or fractures or undergoing major surgical resections within 60 days preceding the first day of drug administration.

5. Presence of any severe or uncontrolled coexisting diseases, including but not limited to:

• Uncontrolled hypertension

• History of interstitial lung disease or non-infectious pneumonia

• Active hepatitis B or C, syphilis, or other active and uncontrolled infections

• Cardiac insufficiency (NYHA=2)

• Renal dysfunction requiring dialysis

• Active autoimmune disease

• History of acquired or congenital immunodeficiency diseases

6. Occurrence of serious arterial/venous thrombotic events within 6 months prior to the first day of drug administration.

7. History of psychotropic substance abuse or inability to quit, or patients with psychotic disorders.

8. Allergy to study drugs.

9. Patients deemed unsuitable for participation due to severe comorbidities or other reasons determined by the investigators.

Related Conditions & MeSH terms

• Carcinoma, Squamous Cell
• Esophageal Neoplasms
• Esophageal Squamous Cell Carcinoma

Intervention

Drug:
• PD-1inhibitor
PD-1 inhibitor, Q3W, until disease progression or unacceptable toxicity or treatment reaches 1 year
• nab-paclitaxel + cisplatin
Induction phase: nab-paclitaxel + cisplatin, Q3W × 2 cycles; Concurrent ICRT phase: nab-paclitaxel + cisplatin, QW × 5 cycles

Radiation:
• Radiotherapy
Primary tumor and metastatic lymph nodes, DT:45-50Gy/25fx, starting within 4 weeks following the completion of the last induction immunochemotherapy cycle

Locations

Country	Name	City	State
China	Shanghai Chest Hospital	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Shanghai Chest Hospital

Country where clinical trial is conducted

China, 

References & Publications (9)

Hulshof MCCM, Geijsen ED, Rozema T, Oppedijk V, Buijsen J, Neelis KJ, Nuyttens JJME, van der Sangen MJC, Jeene PM, Reinders JG, van Berge Henegouwen MI, Thano A, van Hooft JE, van Laarhoven HWM, van der Gaast A. Randomized Study on Dose Escalation in Definitive Chemoradiation for Patients With Locally Advanced Esophageal Cancer (ARTDECO Study). J Clin Oncol. 2021 Sep 1;39(25):2816-2824. doi: 10.1200/JCO.20.03697. Epub 2021 Jun 8. — View Citation

Kelly RJ, Ajani JA, Kuzdzal J, Zander T, Van Cutsem E, Piessen G, Mendez G, Feliciano J, Motoyama S, Lievre A, Uronis H, Elimova E, Grootscholten C, Geboes K, Zafar S, Snow S, Ko AH, Feeney K, Schenker M, Kocon P, Zhang J, Zhu L, Lei M, Singh P, Kondo K, Cleary JM, Moehler M; CheckMate 577 Investigators. Adjuvant Nivolumab in Resected Esophageal or Gastroesophageal Junction Cancer. N Engl J Med. 2021 Apr 1;384(13):1191-1203. doi: 10.1056/NEJMoa2032125. Erratum In: N Engl J Med. 2023 Feb 16;388(7):672. — View Citation

Li C, Zhao S, Zheng Y, Han Y, Chen X, Cheng Z, Wu Y, Feng X, Qi W, Chen K, Xiang J, Li J, Lerut T, Li H. Preoperative pembrolizumab combined with chemoradiotherapy for oesophageal squamous cell carcinoma (PALACE-1). Eur J Cancer. 2021 Feb;144:232-241. doi: 10.1016/j.ejca.2020.11.039. Epub 2020 Dec 26. — View Citation

Shah MA, Bennouna J, Doi T, Shen L, Kato K, Adenis A, Mamon HJ, Moehler M, Fu X, Cho BC, Bordia S, Bhagia P, Shih CS, Desai A, Enzinger P. KEYNOTE-975 study design: a Phase III study of definitive chemoradiotherapy plus pembrolizumab in patients with esophageal carcinoma. Future Oncol. 2021 Apr;17(10):1143-1153. doi: 10.2217/fon-2020-0969. Epub 2021 Feb 3. — View Citation

Spigel DR, Faivre-Finn C, Gray JE, Vicente D, Planchard D, Paz-Ares L, Vansteenkiste JF, Garassino MC, Hui R, Quantin X, Rimner A, Wu YL, Ozguroglu M, Lee KH, Kato T, de Wit M, Kurata T, Reck M, Cho BC, Senan S, Naidoo J, Mann H, Newton M, Thiyagarajah P, Antonia SJ. Five-Year Survival Outcomes From the PACIFIC Trial: Durvalumab After Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer. J Clin Oncol. 2022 Apr 20;40(12):1301-1311. doi: 10.1200/JCO.21.01308. Epub 2022 Feb 2. Erratum In: J Clin Oncol. 2022 Jun 10;40(17):1965. — View Citation

Sun JM, Shen L, Shah MA, Enzinger P, Adenis A, Doi T, Kojima T, Metges JP, Li Z, Kim SB, Cho BC, Mansoor W, Li SH, Sunpaweravong P, Maqueda MA, Goekkurt E, Hara H, Antunes L, Fountzilas C, Tsuji A, Oliden VC, Liu Q, Shah S, Bhagia P, Kato K; KEYNOTE-590 Investigators. Pembrolizumab plus chemotherapy versus chemotherapy alone for first-line treatment of advanced oesophageal cancer (KEYNOTE-590): a randomised, placebo-controlled, phase 3 study. Lancet. 2021 Aug 28;398(10302):759-771. doi: 10.1016/S0140-6736(21)01234-4. Erratum In: Lancet. 2021 Nov 20;398(10314):1874. — View Citation

Wang Z, Shao C, Wang Y, Duan H, Pan M, Zhao J, Wang J, Ma Z, Li X, Yan X. Efficacy and safety of neoadjuvant immunotherapy in surgically resectable esophageal cancer: A systematic review and meta-analysis. Int J Surg. 2022 Aug;104:106767. doi: 10.1016/j.ijsu.2022.106767. Epub 2022 Jul 14. — View Citation

Yu R, Wang W, Li T, Li J, Zhao K, Wang W, Liang L, Wu H, Ai T, Huang W, Li L, Yu W, Wei C, Wang Y, Shen W, Xiao Z. RATIONALE 311: tislelizumab plus concurrent chemoradiotherapy for localized esophageal squamous cell carcinoma. Future Oncol. 2021 Nov;17(31):4081-4089. doi: 10.2217/fon-2021-0632. Epub 2021 Jul 16. — View Citation

Zhu Y, Wen J, Li Q, Chen B, Zhao L, Liu S, Yang Y, Wang S, Lv Y, Li J, Zhang L, Hu Y, Liu M, Xi M. Toripalimab combined with definitive chemoradiotherapy in locally advanced oesophageal squamous cell carcinoma (EC-CRT-001): a single-arm, phase 2 trial. Lancet Oncol. 2023 Apr;24(4):371-382. doi: 10.1016/S1470-2045(23)00060-8. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first	Assessed up to 60 months
Primary	Treatment completion rate	The Treatment Completion Rate is defined as the percentage of patients who successfully completed concurrent immuno-chemoradiotherapy.	1 year
Secondary	Objective response rate	Objective response rate (ORR), defined as the proportion of patients with a complete response or partial response after Immuno-Chemoradiotherapy according to Response Evaluation Criteria in Solid Tumors (RECIST)	1 year
Secondary	Overall survival	From date of randomization until the date of death from any cause	Assessed up to 60 months
Secondary	Incidence of Adverse events (AE) or severe adverse events (SAE)	Adverse events (AE) or severe adverse events (SAE) occurring within 3 months post-radiotherapy, and the incidence of treatment discontinuation due to AE/SAE	1 year